Browsing Pathways

Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.

Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.

Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.

The biosynthesis of glutathione starts with the introduction of L-glutamic acid through either a glutamate:sodium symporter, glutamate / aspartate : H+ symporter GltP or a glutamate / aspartate ABC transporter. Once in the cytoplasm, L-glutamice acid reacts with L-cysteine through an ATP glutamate-cysteine ligase resulting in gamma-glutamylcysteine. This compound reacts which Glycine through an ATP driven glutathione synthetase thus catabolizing Glutathione. This compound is metabolized through a spontaneous reaction with an oxidized glutaredoxin resulting in a reduced glutaredoxin and an oxidized glutathione. This compound is reduced by a NADPH glutathione reductase resulting in a glutathione. Glutathione can then be degraded into various different glutathione containing compounds by reacting with a napthalene or Bromobenzene-2,3-oxide through a glutathione S-transferase.

Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.

The glyoxylate cycle starts with the interaction of Acetyl-Coa with a water molecule and Oxalacetic acid interact through a Citrate synthase resulting in a release of a coenzyme a and citric acid. The citric acid gets dehydrated through a citrate hydro-lyase resulting in the release of a water molecule and cis-Aconitic acid. The cis-Aconitic acid is then hydrated in an reversible reaction through an aconitate hydratase resulting in an Isocitric acid. The isocitric acid then interacts in a reversible reaction through isocitrate lyase resulting in the release of a succinic acid and a glyoxylic acid. The glyoxylic acid then reacts in a reversible reaction with an acetyl-coa, and a water molecule in a reversible reaction, resulting in a release of a coenzyme A, a hydrogen ion and an L-malic acid. The L-malic acid interacts in a reversible reaction through a NAD driven malate dehydrogenase resulting in the release of NADH, a hydrogen ion and an Oxalacetic acid.

Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.

The biosynthesis of a enterobacterial common antigen can begin with a di-trans,octa-cis-undecaprenyl phosphate interacts with a Uridine diphosphate-N-acetylglucosamine through undecaprenyl-phosphate α-N-acetylglucosaminyl transferase resulting in a N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol and a Uridine 5'-monophosphate. The N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol then reacts with an UDP-ManNAcA from the Amino sugar and nucleotide sugar metabolism pathway. This reaction is metabolized by a UDP-N-acetyl-D-mannosaminuronic acid transferase resulting in a uridine 5' diphosphate, a hydrogen ion and a Undecaprenyl N-acetyl-glucosaminyl-N-acetyl-mannosaminuronate-4-acetamido-4,6-dideoxy-D-galactose pyrophosphate. Glucose 1 phosphate can be metabolize by interacting with a hydrogen ion and a thymidine 5-triphosphate by either reacting with a dTDP-glucose pyrophosphorylase or a dTDP-glucose pyrophosphorylase 2 resulting in the release of a pyrophosphate and a dTDP-D-glucose. The latter compound is then dehydrated through an dTDP-glucose 4,6-dehydratase 2 resulting in water and dTDP-4-dehydro-6-deoxy-D-glucose. The latter compound interacts with L-glutamic acid through a dTDP-4-dehydro-6-deoxy-D-glucose transaminase resulting in the release of oxoglutaric acid and dTDP-thomosamine. The latter compound interacts with acetyl-coa through a dTDP-fucosamine acetyltransferase resulting in a Coenzyme A, a hydrogen Ion and a TDP-Fuc4NAc. Undecaprenyl N-acetyl-glucosaminyl-N-acetyl-mannosaminuronate-4-acetamido-4,6-dideoxy-D-galactose pyrophosphate then interacts with a TDP--Fuc4NAc through a 4-acetamido-4,6-dideoxy-D-galactose transferase resulting in a hydrogen ion, a dTDP and a Undecaprenyl N-acetyl-glucosaminyl-N-acetyl-mannosaminuronate-4-acetamido-4,6-dideoxy-D-galactose pyrophosphate. This compound is then transported through a protein wzxE into the periplasmic space so that it can be incorporated into the outer membrane.

The biosynthesis of isoprenoids starts with a D-glyceraldehyde 3-phosphate interacting with a hydrogen ion through a 1-deoxyxylulose-5-phosphate synthase resulting in a carbon dioxide and 1-Deoxy-D-xylulose. The latter compound then interacts with a hydrogen ion through a NADPH driven 1-deoxy-D-xylulose 5-phosphate reductoisomerase resulting in a NADP and a 2-C-methyl-D-erythritol 4-phosphate. The latter compound then interacts with a cytidine triphosphate and a hydrogen ion through a 4-diphosphocytidyl-2C-methyl-D-erythritol synthase resulting in a pyrophosphate and a 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol. The latter compound is then phosphorylated through an ATP driven 4-diphosphocytidyl-2-C-methylerythritol kinase resulting in a release of an ADP, a hydrogen ion and a 2-phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol. The latter compound then interacts with a 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase resulting in the release of a 2-C-methyl-D-erythritol-2,4-cyclodiphosphate resulting in the release of a cytidine monophosphate and 2-C-methyl-D-erythritol-2,4-cyclodiphosphate. The latter compound then interacts with a reduced flavodoxin through a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase resulting in the release of a water molecule, a hydrogen ion, an oxidized flavodoxin and a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate. The compound 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate can interact with an NADPH,a hydrogen ion through a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase resulting in a NADP, a water molecule and either a Dimethylallylpyrophosphate or a Isopentenyl pyrophosphate. These two last compounds can be are isomers that can be produced through a isopentenyl diphosphate isomerase. Dimethylallylpyrophosphate interacts with the isopentenyl pyrophosphate through a geranyl diphosphate synthase / farnesyl diphosphate synthase resulting in a pyrophosphate and a geranyl--PP. The latter compound interacts with a Isopentenyl pyrophosphate through a geranyl diphosphate synthase / farnesyl diphosphate synthase resulting in the release of a pyrophosphate and a farnesyl pyrophosphate. The latter compound interacts with isopentenyl pyrophosphate either through a undecaprenyl diphosphate synthase resulting in a release of a pyrophosphate and a di-trans,octa-cis-undecaprenyl diphosphate or through a octaprenyl diphosphate synthase resulting in a pyrophosphate and an octaprenyl diphosphate

Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.